咖啡酸酯类衍生物作为神经保护剂的构效关系研究

doi:10.5246/jcps.2019.09.059

摘要/Abstract

摘要：

本研究以多活性的咖啡酸苯乙酯为先导化合物, 设计和合成了一系列咖啡酸酯类衍生物, 在细胞水平上测定了化合物的抗炎、抗氧化活性, 并利用平行人工膜透过实验评价了化合物的血脑屏障透过能力。结果显示, CAPE分子结构中的酚羟基、双键的结构改变对化合物的神经保护活性有重要影响, 本文对相关构效关系进行了初步总结。另外, 改造后的化合物在血脑屏障透过能力方面有显著提升。这些结果为今后CAPE的结构优化提供了重要依据。

关键词: 咖啡酸苯乙酯, 神经保护, 抗炎, 抗氧化, 血脑屏障通透性

Abstract:

In the present study, novel ester derivatives of CAPE were designed and synthesized as neuroprotective agents. The anti-inflammatory and antioxidant activities of these compounds were evaluated at the cellular level, while the blood-brain barrier (BBB) permeability was predicted by parallel artificial membrane permeability assay (PAMPA). The results revealed that phenolic hydroxyl groups and double bonds in the structure of CAPE had important effects on neuroprotective activities. Accordingly,a preliminary structure-activity relationship was summarized in this paper. In addition, we observed a significant improvement on BBB permeability. These results provided important references for the structural modification and optimization of CAPE in the future.

Key words: Caffeic acid phenethyl esters, Neuroprotective activity, Anti-inflammation, Anti-oxidation, BBB permeability

中图分类号:

R914

Supporting:

吴柏林, 郝亚萌, 陈颖, 刘乾, 田超, 张志丽, 刘俊义, 王孝伟. 咖啡酸酯类衍生物作为神经保护剂的构效关系研究[J]. 中国药学(英文版), 2019, 28(9): 615-626.

Bolin Wu, Yameng Hao, Ying Chen, Qian Liu, Chao Tian, Zhili Zhang, Junyi Liu, Xiaowei Wang. Studies on the structure-activity relationship of caffeate derivatives as neuroprotective agents[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(9): 615-626.

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